Up-regulatation of CYP3A expression through pregnent X receptor by praeruptorin D isolated from Peucedanum praeruptorum Dunn
| Autor: | Shao-Yi Kuang, Yu Zeng, Min Huang, Hui-Chang Bi, Yuhua Li, Ling Huang, Rui-Ming Li, Yitao Wang, Li Zhang |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Transcriptional Activation Receptors Steroid CYP3A Herb-Drug Interactions Gene Expression Pharmacology Biology Cell Line Mice Transactivation Coumarins Drug Discovery Gene expression Animals Cytochrome P-450 CYP3A Humans RNA Messenger Medicine Chinese Traditional Mice Inbred BALB C Pregnane X receptor CYP3A4 Plant Extracts Pregnane X Receptor Membrane Proteins Transfection Up-Regulation Nuclear receptor Cell culture Hepatocytes Apiaceae |
| Zdroj: | Journal of Ethnopharmacology. 148:596-602 |
| ISSN: | 0378-8741 |
| DOI: | 10.1016/j.jep.2013.05.008 |
| Popis: | Ethnopharmacological relevance Qianhu, the dried roots of Peucedanum praeruptorum DUNN (Umbelliferae), is a well-known traditional Chinese medicinal herb which was officially listed in the Chinese Pharmacopoeia. Praeruptorin D (PD) is one of the major active constituents of Peucedanum praeruptorum Dunn (Qianhu). The Pregnane X receptor (PXR) is an orphan nuclear receptor and plays a pivotal role in the activation of human cytochrome P450 3A4 (CYP3A4) gene. Aim of the study The purpose of this study was to investigate the effect of PD on the PXR-mediated transactivation of CYP3A4, and thus to predict potential herb–drug interactions between PD, Qianhu, and the other co-administered drugs that metabolized by CYP3A4. Materials and methods The effect of PD on the Cyp3a11 , mPXR mRNA expression in mice primary hepatocytes was measured using real-time PCR. The gene expression, protein expression, and catalytic activity of CYP3A4 in the LS174T cells after transfected with PXR expression plasmids were determined by real-time PCR, Western blot analysis, and LC–MS/MS based CYP3A4 substrate assay. Results The results revealed that the level of Cyp3a 11 gene expression in mice primary hepatocytes was significantly increased by PD, but PD cannot induce the mPXR gene expression. On the other hand, CYP3A4 mRNA, protein expression and functional activity in PXR-over-expression LS174T cells were significantly increased by PD through PXR-mediated pathway; conversely, no significant change was found in the untransfected cells. Conclusions These findings suggest that PD can significantly up-regulate CYP3A4 expression and activity via the PXR-mediated pathway and this should be taken into consideration to predict any potential herb–drug interactions when PD and Peucedanum praeruptorum Dunn are co-administered with other drugs. |
| Databáze: | OpenAIRE |
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